Background: Spodoptera littoralis (Boisd.) is a prominent agricultural insect pest that has developed resistance to a variety of insecticide classes. In this study, the resistance of three field strains of S. littoralis, collected over three consecutive seasons (2018 to 2020) from three Egyptian Governorates (El-Fayoum, Behera and Kafr El-Shiekh), to six insecticides was monitored. Methods: Laboratory bioassays were carried out using the leaf-dipping method to examine the susceptibility of the laboratory and field strains to the tested insecticides. Activities of detoxification enzymes were determined in an attempt to identify resistance mechanisms. Results: The results showed that LC₅₀ values of the field strains ranged from 0.0089 to 132.24 mg/L, and the corresponding resistance ratio (RR) ranged from 0.17 to 4.13-fold compared with the susceptible strain. Notably, low resistance developed to spinosad in all field strains, and very low resistance developed to alpha-cypermethrin and chlorpyrifos. On the other hand, no resistance developed to methomyl, hexaflumeron or Bacillus thuringiensis. The determination of detoxification enzymes, including carboxylesterases (α- and β-esterase), mixed function oxidase (MFO) and glutathione-S-transferase (GST), or the target site of acetylcholinesterase (AChE), revealed that the three field strains had significantly different activity levels compared with the susceptible strain. Conclusion: Our findings, along with other tactics, are expected to help with the resistance management of S. littoralis in Egypt.